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1.
Jt Dis Relat Surg ; 35(3): 654-661, 2024 Aug 14.
Article in English | MEDLINE | ID: mdl-39189576

ABSTRACT

OBJECTIVES: This study aimed to evaluate the biomechanical and histological effects of fluoroquinolones on surgically repaired tendon healing. MATERIALS AND METHODS: The Achilles tendons of 40 Wistar rats (mean weight: 213.5 g; range 201 to 242 g) were bilaterally surgically cut and repaired. The rats were randomly divided into four groups: the first and third groups were designated as control groups and did not receive drug therapy, whereas the second and fourth groups received 300 mg/kg ciprofloxacin for a week after the surgical procedure. The first and second groups had both tendons dissected at the end of the first week, while the third and fourth groups were dissected at the end of the third week. The left tendons were examined biomechanically, while the right tendons were examined histologically. RESULTS: Statistical analysis revealed that the mean maximum tensile forces of tendons in the first and second groups were 5.2±1.84 N (range, 2.9 to 8.5 N) and 11.1±2.65 N (range, 7.3 to 13.9 N), respectively, which was found to be statistically significant (p< 0.05). At the end of the third week, mean maximum tensile forces of the third and fourth groups were determined to be 20.7±5.0 N (range, 22.1 to 29.8 N) and 28.7±4.6 N (range, 22.1 to 36.8 N), respectively, which was also statistically significant (p< 0.05). Histologically, our results were compatible. CONCLUSION: This study demonstrated that ciprofloxacin did not exhibit the expected adverse effects on surgically repaired tendon healing in the early stages but likely contributed to healing in the short term by affecting the inflammatory phase.


Subject(s)
Achilles Tendon , Ciprofloxacin , Rats, Wistar , Tendon Injuries , Tensile Strength , Wound Healing , Animals , Wound Healing/drug effects , Achilles Tendon/surgery , Achilles Tendon/injuries , Achilles Tendon/drug effects , Achilles Tendon/pathology , Rats , Ciprofloxacin/adverse effects , Ciprofloxacin/pharmacology , Tensile Strength/drug effects , Tendon Injuries/surgery , Tendon Injuries/drug therapy , Tendon Injuries/pathology , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/adverse effects , Biomechanical Phenomena/drug effects , Male , Fluoroquinolones/pharmacology , Fluoroquinolones/adverse effects
2.
Commun Biol ; 7(1): 1035, 2024 Aug 23.
Article in English | MEDLINE | ID: mdl-39179666

ABSTRACT

Tuberculosis (TB), caused by Mycobacterium tuberculosis, remains a serious threat to global public health. Fluoroquinolones (FQs) are effective against M. tuberculosis; however, resistant strains have limited their efficacy. Mycobacterium fluoroquinolone resistance protein A (MfpA) confers intrinsic resistance to FQs; however, its regulatory mechanisms remain largely unknown. Using M. smegmatis as a model, we investigated whether MfpC is necessary for FQ susceptibility. MfpC mutants were sensitive to moxifloxacin, indicating that MfpC is involved in FQ susceptibility. By testing the mfpC inactivation phenotype in different mutants and using mycobacterial protein fragment complementation, we demonstrated that the function of MfpC depends on its interactions with MfpB. Guanine nucleotide exchange assays and site-directed mutagenesis confirmed that MfpC acts as a guanine nucleotide exchange factor to regulate MfpB. We propose that MfpB influences MfpA at the translational level. In summary, we reveal the role of MfpC in regulating the function of MfpA in FQ resistance.


Subject(s)
Bacterial Proteins , Fluoroquinolones , Mycobacterium smegmatis , Mycobacterium smegmatis/genetics , Mycobacterium smegmatis/metabolism , Mycobacterium smegmatis/drug effects , Fluoroquinolones/pharmacology , Bacterial Proteins/metabolism , Bacterial Proteins/genetics , Drug Resistance, Bacterial/genetics , Guanine Nucleotide Exchange Factors/metabolism , Guanine Nucleotide Exchange Factors/genetics , Microbial Sensitivity Tests , Anti-Bacterial Agents/pharmacology , Gene Expression Regulation, Bacterial , Mutation
3.
Environ Geochem Health ; 46(9): 363, 2024 Aug 10.
Article in English | MEDLINE | ID: mdl-39126534

ABSTRACT

Fluoroquinolone antibiotics have been extensively used in clinical treatments for human and animal diseases. However, their long-term presence in the environment increases the risk of producing resistance genes and creates a potential threat to ecosystems and the health of humans and animals. Batch equilibrium experiments were utilized to investigate the adsorption and retention behavior and mechanism of the quinolone antibiotic enrofloxacin (ENR) in farmland soil in North China. The adsorption and desorption kinetics of ENR in soil were best fitted by pseudo-second-order model (R2 > 0.999). Both the adsorption and desorption processes of ENR in soil reached equilibrium in 1 h. The desorption amounts of ENR were significantly lower than the adsorption amounts, with the hysteresis coefficient (HI) being less than 0.7. The adsorption thermodynamic process of ENR followed the Linear and Freundlich models (0.965 < R2 < 0.985). Hydrophobic distribution and heterogeneous multimolecular layer adsorption were identified as critical factors in the adsorption process. The adsorption amount of ENR gradually decreased with increasing temperature and the initial concentration of ENR. The adsorption rate of ENR was above 80%, while the desorption rate remained below 15%, indicating strong retention ability. The adsorption rate of ENR in soil decreased with increasing pH, the adsorption rate reached 98.3% at pH 3.0 but only 31.5% at pH 11. The influence of coexisting ions on adsorption primarily depended on their properties, such as ion radius, ionic strength, and hydrolysis properties, and the inhibition of adsorption increased with increasing ionic strength. These findings contribute to understanding the fate and risk of veterinary antibiotics in loess soil in North China.


Subject(s)
Anti-Bacterial Agents , Enrofloxacin , Soil Pollutants , Soil , Enrofloxacin/chemistry , Adsorption , Soil Pollutants/chemistry , Hydrogen-Ion Concentration , Anti-Bacterial Agents/chemistry , Soil/chemistry , China , Farms , Fluoroquinolones/chemistry , Kinetics , Ions/chemistry
5.
Anal Chim Acta ; 1320: 342999, 2024 Sep 01.
Article in English | MEDLINE | ID: mdl-39142779

ABSTRACT

BACKGROUND: Fluoroquinolones (FQs) are widely used for their excellent antimicrobial properties, yet their release into aquatic environments pose risks to ecosystems and public health. The accurate monitoring and analysis of FQs present challenges due to their low concentrations and the complex matrices found in actual environmental samples. To address the need for auto-pretreatment and on-line instrumental analysis, developing new microextraction materials and protocols is crucial. Such advancements will provide better analytical assurance for the effective extraction and determination of FQs at trace levels, which is of great significance to environmental protection and human health. RESULTS: In this work, we presented a Co2+ mediated paper-based molecularly imprinted polymer chip (CMC@Co-MIP), combined with UPLC analysis, to develop an effective analytical method for identifying and quantifying trace amounts of ciprofloxacin (CIP) and enrofloxacin (ENR) in water samples. Notably, the addition of Co2+ in CMC@Co-MIP helped to capture the template molecule CIP through coordination before imprinting, which significantly improved the ordering of the imprinted cavities. CMC@Co-MIP exhibited a maximum adsorption capacity up to 500.20 mg g-1 with an imprinting factor of 4.12, surpassing previous reports by a significant margin. Furthermore, the enrichment mechanism was extensively analyzed by various characterization techniques. The developed method showed excellent repeatability and reproducibility (RSD < 13.0 %) with detection limits ranging from 0.15 to 0.21 µg L-1 and recoveries ranging from 64.9 % to 102.3 % in real spiked water samples. SIGNIFICANCE: We developed a novel microextraction paper-based chip based on Co2+ mediation, which effectively improved the selectivity and convenience of extracting FQs. This breakthrough allowed the chip to have a high enrichment efficiency as well as provide a robust on-line instrumental program. It also confirms that the imprinting scheme based on metal ion coordination is a high-performance strategy.


Subject(s)
Cobalt , Fluoroquinolones , Molecularly Imprinted Polymers , Paper , Water Pollutants, Chemical , Cobalt/analysis , Cobalt/chemistry , Water Pollutants, Chemical/analysis , Molecularly Imprinted Polymers/chemistry , Fluoroquinolones/analysis , Molecular Imprinting , Limit of Detection , Adsorption , Solid Phase Microextraction/methods
6.
Molecules ; 29(15)2024 Jul 27.
Article in English | MEDLINE | ID: mdl-39124943

ABSTRACT

Cancer is the second leading cause of death in the world following cardiovascular disease. Its treatment, including radiation therapy and surgical removal of the tumour, is based on pharmacotherapy, which prompts a constant search for new and more effective drugs. There are high costs associated with designing, synthesising, and marketing new substances. Drug repositioning is an attractive solution. Fluoroquinolones make up a group of synthetic antibiotics with a broad spectrum of activity in bacterial diseases. Moreover, those compounds are of particular interest to researchers as a result of reports of their antiproliferative effects on the cells of the most lethal cancers. This article presents the current progress in the development of new fluoroquinolone derivatives with potential anticancer and cytotoxic activity, as well as structure-activity relationships, along with possible directions for further development.


Subject(s)
Antineoplastic Agents , Fluoroquinolones , Fluoroquinolones/chemistry , Fluoroquinolones/pharmacology , Humans , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Antineoplastic Agents/chemical synthesis , Structure-Activity Relationship , Neoplasms/drug therapy , Animals , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Drug Repositioning , Cell Proliferation/drug effects
7.
BMC Infect Dis ; 24(1): 856, 2024 Aug 23.
Article in English | MEDLINE | ID: mdl-39179971

ABSTRACT

BACKGROUND: Fluoroquinolones are the most commonly prescribed antibiotics. Because of their known tendency to drive antimicrobial resistance, their prescribing patterns need to be more restricted. This study aimed to describe the clinical practice of fluoroquinolone prescription, dose adjustments for renal impairment patients and bacterial resistance profiles, eventually providing evidence-based recommendations to optimize antibiotic prescribing practices in the local population. METHODS: This retrospective, cross-sectional study was conducted at An-Najah National University Hospital in Palestine. The data were collected from admitted patients who were given ciprofloxacin or levofloxacin from July 2021 to June 2023. Data from 692 inpatients across various hospital departments were examined (409 for levofloxacin and 283 for ciprofloxacin). Statistical analysis was performed via IBM SPSS version 23.0 to summarize the demographic, clinical, and epidemiological data. RESULTS: The sociodemographic profile revealed diverse age distributions, with 25.4% and 39% older than 50 years for ciprofloxacin and levofloxacin, respectively. Ciprofloxacin was predominantly used in the oncology department (28.2%), with surgical prophylaxis (22.6%) and febrile or afebrile neutropenia (21.1%) being the most common indications. Levofloxacin was predominantly used in the medical ward (45.7%), mainly for lower respiratory tract infection (58.8%) and prophylaxis for bone marrow transplantation (16.5%). Enterococcus and methicillin-resistant Staphylococcus aureus were the most commonly isolated pathogens, with 62.5% of the isolates demonstrating resistance to ciprofloxacin. Moreover, extended-spectrum beta-lactamase-producing Enterobacterales were the most common pathogen isolated, with 33.3% being resistant to levofloxacin. Statistical analysis revealed a significant association between the choice of antibiotic and the approach to therapy. Levofloxacin was significantly more likely than ciprofloxacin to be used as empiric therapy (p < 0.001), whereas ciprofloxacin was more likely to be used as targeted therapy (p < 0.001). CONCLUSIONS: This study investigated prescribing practices and resistance to levofloxacin and ciprofloxacin in a large hospital in a developing country. According to the bacterial resistance profiles, we conclude that there is a need for hospital departments to exercise greater restraint on the use of these antibiotics. To this end, further studies addressing the clinical efficacy of fluoroquinolones against the current treatment guidelines to evaluate their appropriateness should be carried out.


Subject(s)
Anti-Bacterial Agents , Fluoroquinolones , Levofloxacin , Tertiary Care Centers , Humans , Retrospective Studies , Cross-Sectional Studies , Male , Middle Aged , Female , Tertiary Care Centers/statistics & numerical data , Anti-Bacterial Agents/therapeutic use , Anti-Bacterial Agents/pharmacology , Adult , Fluoroquinolones/therapeutic use , Fluoroquinolones/pharmacology , Aged , Levofloxacin/therapeutic use , Levofloxacin/pharmacology , Ciprofloxacin/therapeutic use , Ciprofloxacin/pharmacology , Drug Resistance, Bacterial , Young Adult , Adolescent , Aged, 80 and over , Practice Patterns, Physicians'/statistics & numerical data , Microbial Sensitivity Tests , Middle East/epidemiology , Bacteria/drug effects , Bacteria/isolation & purification
8.
Sci Rep ; 14(1): 19719, 2024 08 24.
Article in English | MEDLINE | ID: mdl-39181942

ABSTRACT

Fluoroquinolone resistance is a major challenge in treating Multidrug-Resistant Tuberculosis globally. The GenoType MTBDRsl Ver 2.0, endorsed by the WHO, was used to characterize fluoroquinolone resistance. The fluoroquinolone resistance rates in the MDR-TB, Rifampicin-Resistant TB, and non-MDR-TB were 33%, 16.5%, and 5.4%, respectively. The most common mutation found in fluoroquinolone-resistant isolates was D94G (49.5%) in the gyrA gene. Of the 150 MDR-TB isolates, the prevalence of Extensively Drug-Resistant Tuberculosis and pre-XDR-TB was 1.33% and 30%, respectively. Among the 139 RR-TB isolates, pre-XDR-TB prevalence was 15.8%. The fluoroquinolone resistance rates were 5.12% among the 1230 isoniazid-monoresistant isolates. The study found that MDR-TB and RR-TB have higher risk of fluoroquinolone resistance than non-MDR tuberculosis. Rifampicin-resistant isolates with a mutation at codon S450L have a higher risk (RR = 12.96; 95%CI: 8.34-20.13) of developing fluoroquinolone resistance than isolates with mutations at other codons in the rpoB gene. Isoniazid-resistant isolates with a mutation at codon S315T have a higher risk (RR = 2.09; 95%CI: 1.25-3.50) of developing fluoroquinolone resistance. The study concludes that rapid diagnosis of fluoroquinolone resistance before starting treatment is urgently needed to prevent the spread and increase of resistance and to achieve better treatment outcomes in areas where it is higher.


Subject(s)
Antitubercular Agents , Fluoroquinolones , Mycobacterium tuberculosis , Tuberculosis, Multidrug-Resistant , Humans , Fluoroquinolones/pharmacology , Fluoroquinolones/therapeutic use , Mycobacterium tuberculosis/genetics , Mycobacterium tuberculosis/drug effects , Retrospective Studies , Tuberculosis, Multidrug-Resistant/epidemiology , Tuberculosis, Multidrug-Resistant/drug therapy , Tuberculosis, Multidrug-Resistant/microbiology , Tuberculosis, Multidrug-Resistant/transmission , Tuberculosis, Multidrug-Resistant/genetics , Antitubercular Agents/pharmacology , Antitubercular Agents/therapeutic use , Male , Female , Tuberculosis, Pulmonary/epidemiology , Tuberculosis, Pulmonary/drug therapy , Tuberculosis, Pulmonary/microbiology , Adult , Mutation , Risk Assessment , Middle Aged , Microbial Sensitivity Tests , Rifampin/pharmacology , Rifampin/therapeutic use , Extensively Drug-Resistant Tuberculosis/epidemiology , Extensively Drug-Resistant Tuberculosis/microbiology , Extensively Drug-Resistant Tuberculosis/drug therapy , Drug Resistance, Multiple, Bacterial/genetics , Isoniazid/pharmacology , Isoniazid/therapeutic use , Aged
9.
ACS Nano ; 18(28): 18522-18533, 2024 Jul 16.
Article in English | MEDLINE | ID: mdl-38963059

ABSTRACT

The abuse or misuse of antibiotics in clinical and agricultural settings severely endangers human health and ecosystems, which has raised profound concerns for public health worldwide. Trace detection and reliable discrimination of commonly used fluoroquinolone (FQ) antibiotics and their analogues have consequently become urgent to guide the rational use of antibiotic medicines and deliver efficient treatments for associated diseases. Herein, we report a wearable eye patch integrated with a quadruplex nanosensor chip for noninvasive detection and discrimination of primary FQ antibiotics in tears during routine eyedrop treatment. A set of dual-mode fluorescent nanoprobes of red- or green-emitting CdTe quantum dots integrated with lanthanide ions and a sensitizer, adenosine monophosphate, were constructed to provide an enhanced fluorescence up to 45-fold and nanomolar sensitivity toward major FQs owing to the aggregation-regulated antenna effect. The aggregation-driven, CdTe-Ln(III)-based microfluidic sensor chip is highly specific to FQ antibiotics against other non-FQ counterparts or biomolecular interfering species and is able to accurately discriminate nine types of FQ or non-FQ eyedrop suspensions using linear discriminant analysis. The prototyped wearable sensing detector has proven to be biocompatible and nontoxic to human tissues, which integrates the entire optical imaging modules into a miniaturized, smartphone-based platform for field use and reduces the overall assay time to ∼5 min. The practicability of the wearable eye patch was demonstrated through accurate quantification of antibiotics in a bactericidal event and the continuous profiling of FQ residues in tears after using a typical prescription antibiotic eyedrop. This technology provides a useful supplement to the toolbox for on-site and real-time examination and regulation of inappropriate daily drug use that might potentially lead to long-term antibiotic abuse and has great implications in advancing personal healthcare techniques for the regulation of daily medication therapy.


Subject(s)
Anti-Bacterial Agents , Fluoroquinolones , Quantum Dots , Tears , Wearable Electronic Devices , Humans , Anti-Bacterial Agents/analysis , Tears/chemistry , Tears/drug effects , Fluoroquinolones/analysis , Quantum Dots/chemistry , Tellurium/chemistry , Cadmium Compounds/chemistry , Biocompatible Materials/chemistry , Biocompatible Materials/pharmacology , Fluorescent Dyes/chemistry , Biosensing Techniques , Lab-On-A-Chip Devices
10.
BMJ Open Qual ; 13(3)2024 Jul 24.
Article in English | MEDLINE | ID: mdl-39053916

ABSTRACT

BACKGROUND: The US Food and Drug Administration (FDA) issued a warning in December 2018 regarding an increased risk of aortic aneurysms and aortic dissections associated with fluoroquinolone (FQ) use. This warning specifically targeted older adults and patients with conditions such as hypertension, Marfan syndrome, Ehlers-Danlos syndrome, atherosclerosis, peripheral vascular disease and history of aneurysms. OBJECTIVE: To evaluate the impact of the safety warning on prescribing trends of FQs in the targeted population. METHODS: This cross-sectional study with an interrupted time series (ITS) analysis (January 2018-December 2019) used a 25% random sample of IQVIA PharMetrics® Plus for Academics health plan claims database. The impact of the warning on FQ utilisation was quantified among the targeted population and a non-targeted population. RESULTS: From 2018 to 2019, both study populations saw a decrease in the year-over-year percent change of FQ prescriptions per 100 000 beneficiaries (-11%, from 14 227 to 12 662, targeted; -15%, from 5227 to 4446, non-targeted) and proportion of FQ use versus other antibiotics (from 15.6% to 13.8%, targeted; from 9.4% to 8%, non-targeted). In the targeted population, the ITS analysis did not show a significant trend change, a change in level or postwarning trend in the monthly rate of FQ prescriptions per 1000 beneficiaries. A positive trend change was observed in the non-targeted population (0.07, <0.01-0.13), but there were no significant changes in level or post-warning trend. CONCLUSION: We did not find a change in FQ prescription rates after the warning. The utility of safety advisories as a primary tool for mitigating FQ use in high-risk populations should be revisited.


Subject(s)
Anti-Bacterial Agents , Aortic Aneurysm , Aortic Dissection , Fluoroquinolones , United States Food and Drug Administration , Humans , United States/epidemiology , Cross-Sectional Studies , Aortic Dissection/epidemiology , United States Food and Drug Administration/statistics & numerical data , Aortic Aneurysm/epidemiology , Fluoroquinolones/adverse effects , Fluoroquinolones/therapeutic use , Anti-Bacterial Agents/adverse effects , Anti-Bacterial Agents/therapeutic use , Female , Male , Middle Aged , Aged , Interrupted Time Series Analysis , Practice Patterns, Physicians'/statistics & numerical data , Practice Patterns, Physicians'/trends , Practice Patterns, Physicians'/standards , Drug Prescriptions/statistics & numerical data , Adult
11.
J Med Microbiol ; 73(7)2024 Jul.
Article in English | MEDLINE | ID: mdl-39028256

ABSTRACT

Introduction. Pre-existing fluoroquinolones (FQs) resistance is a major threat in treating multidrug-resistant (MDR) tuberculosis. Sitafloxacin (Sfx) is a new broad-spectrum FQ.Hypothesis. Sfx is more active against drug-resistant Mycobacterium tuberculosis (Mtb) isolates.Aim. To determine whether there is cross-resistance between Sfx and ofloxacin (Ofx), levofloxacin (Lfx) and moxifloxacin (Mfx) in MDR Mtb.Methods. A total of 106 clinical Mtb isolates, including 23 pan-susceptible and 83 MDR strains, were analysed for Sfx, Lfx and Mfx resistance using MIC assay. The isolates were also subjected to whole-genome sequencing to analyse drug-resistant genes.Results. Sfx exhibited the most robust inhibition activity against Mtb clinical isolates, with a MIC50 of 0.0313 µg ml-1 and MIC90 of 0.125 µg ml-1, which was lower than that of Mfx (MIC50 = 0.0625 µg ml-1, MIC90 = 1 µg ml-1) and Lfx (MIC50 = 0.125 µg ml-1, MIC90 = 2 µg ml-1). We determined the tentative epidemiological cut-off values as 0.5 µg ml-1 for Sfx. Also, 8.43% (7/83), 43.37% (36/83), 42.17% (35/83) and 51.81% (43/83) MDR strains were resistant to Sfx, Mfx, Lfx and Ofx, respectively. Cross-resistance between Ofx, Lfx and Mfx was 80.43% (37/46). Only 15.22% (7/46) of the pre-existing FQs resistance isolates were resistant to Sfx. Among the 30 isolates with mutations in gyrA or gyrB, 5 (16.67%) were Sfx resistant. The combination of Sfx and rifampicin could exert partial synergistic effects, and no antagonism between Sfx and six clinically important anti-Mtb antibiotics was evident.Conclusion. Sfx exhibited superior activity against MDR isolates comparing to Lfx and Mfx, and could potentially overcome the majority pre-existing FQs resistance in Mtb strains.


Subject(s)
Antitubercular Agents , Drug Resistance, Multiple, Bacterial , Fluoroquinolones , Levofloxacin , Microbial Sensitivity Tests , Moxifloxacin , Mycobacterium tuberculosis , Tuberculosis, Multidrug-Resistant , Fluoroquinolones/pharmacology , Mycobacterium tuberculosis/drug effects , Mycobacterium tuberculosis/genetics , Moxifloxacin/pharmacology , Levofloxacin/pharmacology , Humans , Tuberculosis, Multidrug-Resistant/microbiology , Tuberculosis, Multidrug-Resistant/drug therapy , Antitubercular Agents/pharmacology , Whole Genome Sequencing
12.
Indian J Tuberc ; 71 Suppl 1: S37-S43, 2024.
Article in English | MEDLINE | ID: mdl-39067953

ABSTRACT

BACKGROUND & OBJECTIVES: The purpose of present study is to analyse the distribution and pattern of genetic mutations in PRE-XDR-TB and extensive drug resistant Mycobacterium tuberculosis (XDR-TB) using second-line line probe assay and to compare them with different parameters. METHOD: Sputum, Lymph node aspirate and cold accesses from patients with rifampicin resistant Tuberculosis were subjected to first line and second line Probe Assay (Genotype MTBDRsl by Hain Life Science, Germany) to assess additional drug resistance to fluroquinolones (Levofloxacin & Moxifloxacin) and Aminoglycosides (Amikacin, Ofloxacin and Kanamycin). The genetic mutation pattern was analysed and compared with demographic, clinical and other parameters. RESULTS: The final study population included 123 fluoroquinolone resistant isolates including 14 isolates with additional second line aminoglycosides drug resistance. The most frequent mutation observed among Gyr A drug resistance mutation was D94G (Gyr A MUT3C, 50/123,40%) corresponding to high level resistance to levofloxacin and moxifloxacin. The most frequent wild type mutant among Gyr A gene locus was WT 3 (85/123,69%). The most common mutation among second line aminoglycoside resistant isolates was at eis WT2 (7/14,50%) followed by rrs MUT 2 (4/14,29%). CONCLUSIONS: GyrA MUT3C (Asp94Gly) was the most common mutation in Gyr A gene locus in M. tuberculosis causing high level levofloxacin and moxifloxacin resistance. Patients with Asp94Gly mutation was significantly associated with underweight body mass index (p = 0.026). This study also observed that history of anti-tuberculosis therapy is a risk factor for FQ drug resistance mutations (p < 0.001).


Subject(s)
Antitubercular Agents , Mutation , Mycobacterium tuberculosis , Humans , Mycobacterium tuberculosis/genetics , Mycobacterium tuberculosis/drug effects , Mycobacterium tuberculosis/isolation & purification , Male , Female , Adult , Antitubercular Agents/pharmacology , Antitubercular Agents/therapeutic use , Tuberculosis, Pulmonary/drug therapy , Tuberculosis, Pulmonary/microbiology , Middle Aged , Extensively Drug-Resistant Tuberculosis/drug therapy , Extensively Drug-Resistant Tuberculosis/microbiology , Microbial Sensitivity Tests , Fluoroquinolones/pharmacology , Fluoroquinolones/therapeutic use , Drug Resistance, Multiple, Bacterial/genetics , Tuberculosis, Multidrug-Resistant/drug therapy , Tuberculosis, Multidrug-Resistant/microbiology , Levofloxacin/pharmacology , Levofloxacin/therapeutic use , Moxifloxacin/therapeutic use , Moxifloxacin/pharmacology , Young Adult
13.
BMC Microbiol ; 24(1): 265, 2024 Jul 18.
Article in English | MEDLINE | ID: mdl-39026143

ABSTRACT

BACKGROUND: The emergence of fluoroquinolone resistance in clinical isolates of Klebsiella pneumoniae is a growing concern. To investigate the mechanisms behind this resistance, we studied a total of 215 K. pneumoniae isolates from hospitals in Bushehr province, Iran, collected between 2017 and 2019. Antimicrobial susceptibility test for fluoroquinolones was determined. The presence of plasmid mediated quinolone resistance (PMQR) and mutations in quinolone resistance-determining region (QRDR) of gyrA and parC genes in ciprofloxacin-resistant K. pneumoniae isolates were identified by PCR and sequencing. RESULTS: Out of 215 K. pneumoniae isolates, 40 were resistant to ciprofloxacin as determined by E-test method. PCR analysis revealed that among these ciprofloxacin-resistant isolates, 13 (32.5%), 7 (17.5%), 40 (100%), and 25 (62.5%) isolates harbored qnrB, qnrS, oqxA and aac(6')-Ib-cr genes, respectively. Mutation analysis of gyrA and parC genes showed that 35 (87.5%) and 34 (85%) of the ciprofloxacin-resistant isolates had mutations in these genes, respectively. The most frequent mutations were observed in codon 83 of gyrA and codon 80 of parC gene. Single gyrA substitution, Ser83→ Ile and Asp87→Gly, and double substitutions, Ser83→Phe plus Asp87→Ala, Ser83→Tyr plus Asp87→Ala, Ser83→Ile plus Asp87→Tyr, Ser83→Phe plus Asp87→Asn and Ser83→Ile plus Asp87→Gly were detected. In addition, Ser80→Ile and Glu84→Lys single substitution were found in parC gene. CONCLUSIONS: Our results indicated that 90% of isolates have at least one mutation in QRDR of gyrA orparC genes, thus the frequency of mutations was very significant and alarming in our region.


Subject(s)
Anti-Bacterial Agents , DNA Gyrase , DNA Topoisomerase IV , Drug Resistance, Bacterial , Klebsiella Infections , Klebsiella pneumoniae , Microbial Sensitivity Tests , Mutation , Plasmids , Quinolones , Klebsiella pneumoniae/genetics , Klebsiella pneumoniae/drug effects , Klebsiella pneumoniae/isolation & purification , DNA Gyrase/genetics , Plasmids/genetics , DNA Topoisomerase IV/genetics , Humans , Anti-Bacterial Agents/pharmacology , Klebsiella Infections/microbiology , Klebsiella Infections/epidemiology , Drug Resistance, Bacterial/genetics , Quinolones/pharmacology , Ciprofloxacin/pharmacology , Iran , Bacterial Proteins/genetics , Prevalence , Fluoroquinolones/pharmacology
14.
J Appl Microbiol ; 135(8)2024 Aug 05.
Article in English | MEDLINE | ID: mdl-39066496

ABSTRACT

AIMS: Staphylococcus aureus is an opportunistic pathogen whose treatment is further complicated by its ability to form biofilms. In this study, we examine the impact of growing S. aureus biofilms on different polymerizing surfaces, specifically agar and agarose, on the pathogen's tolerance to fluoroquinolones. METHODS AND RESULTS: Biofilms of two methicillin-resistant strains of S. aureus were grown on agar or agarose in the presence of the same added nutrients, and their antibiotic susceptibility to two fluoroquinolones, moxifloxacin (MXF) and delafloxacin (DLX), were measured. We also compared the metabolism and extracellular polymeric substances (EPS) production of biofilms that were grown on agar and agarose. CONCLUSIONS: Biofilms that were grown on agarose were consistently more susceptible to antibiotics than those grown on agar. We found that in biofilms that were grown on agar, extracellular protein composition was higher, and adding EPS to agarose-grown biofilms increased their tolerance to DLX to levels that were comparable to agar-grown biofilms.


Subject(s)
Agar , Anti-Bacterial Agents , Biofilms , Fluoroquinolones , Microbial Sensitivity Tests , Sepharose , Staphylococcus aureus , Biofilms/drug effects , Biofilms/growth & development , Fluoroquinolones/pharmacology , Anti-Bacterial Agents/pharmacology , Staphylococcus aureus/drug effects , Staphylococcus aureus/physiology , Staphylococcus aureus/growth & development , Culture Media/chemistry , Moxifloxacin/pharmacology , Methicillin-Resistant Staphylococcus aureus/drug effects , Methicillin-Resistant Staphylococcus aureus/physiology
15.
J Mater Chem B ; 12(31): 7626-7634, 2024 Aug 07.
Article in English | MEDLINE | ID: mdl-39005154

ABSTRACT

The achievement of smart pharmaceuticals whose bioactivity can be spatiotemporally controlled by light stimuli is known as photopharmacology, an emerging area aimed at improving the therapeutic outcome and minimizing side effects. This is especially attractive for antibiotics, for which the inevitable development of multidrug resistance and the dwindling of new clinically approved drugs represent the main drawbacks. Here, we show that nitrosation of the fluoroquinolone norfloxacin (NF), a broad-spectrum antibiotic, leads to the nitrosated bioconjugate NF-NO, which is inactive at the typical minimum inhibitory concentration of NF. Irradiation of NF-NO with visible blue light triggers the simultaneous release of NF and nitric oxide (NO). The photouncaging process is accompanied by the revival of the typical fluorescence emission of NF, quenched in NF-NO, which acts as an optical reporter. This permits the real-time monitoring of the photouncaging process, even within bacteria cells where antibacterial activity is switched on exclusively upon light irradiation. The mechanism of photorelease seems to occur through a two-step hopping electron transfer mediated by the lowest triplet state of NF-NO and the phosphate buffer ions or aminoacids such as tyrosine. Considering the well-known role of NO as an "unconventional" antibacterial, the NF-NO conjugate may represent a potential bimodal antibacterial weapon activatable on demand with high spatio-temporal control.


Subject(s)
Anti-Bacterial Agents , Nitric Oxide , Norfloxacin , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Nitric Oxide/metabolism , Norfloxacin/pharmacology , Norfloxacin/chemistry , Fluorescence , Photochemical Processes , Fluoroquinolones/chemistry , Fluoroquinolones/pharmacology , Microbial Sensitivity Tests , Light , Molecular Structure , Escherichia coli/drug effects
16.
Environ Sci Technol ; 58(31): 13918-13928, 2024 Aug 06.
Article in English | MEDLINE | ID: mdl-39038112

ABSTRACT

Garenoxacin (GRNX) is a novel des-F(6)-fluoroquinolone on the horizon; thus, its fate and risk in the aquatic environment deserve attention. This study systematically investigated, for the first time, the phototransformation of GRNX under simulated and natural sunlight and assessed the ecotoxicity of its photodegradation products. Phototransformation of GRNX was observed to depend strongly on its ionization state, with direct photolysis and self-sensitized photolysis having comparable contributions for the cationic and zwitterionic species, while the latter dominated for the anionic species. Singlet oxygen generated via the self-sensitized photolysis of GRNX was the major reactive oxygen species in its photodegradation. Phototransformation of GRNX in different ionization states followed distinct pathways, with defluorination of the difluoromethyl group occurring only for the zwitterionic and anionic species. GRNX photodegradation in natural water could be described by a simple kinetic model based on the measured steady-state concentrations of 1O2 and ·OH. Toxicity tests with Vibrio fischeri and Chlorella vulgaris consistently indicate that the generation of hydroxylation and decarboxylation products during photodegradation of GRNX increased the acute toxicity. These findings not only provide insights into the fate of GRNX in sunlit surface water but also reveal the potentially significant risk of its photodegradation products to the aquatic ecosystem.


Subject(s)
Fluoroquinolones , Photolysis , Sunlight , Fluoroquinolones/chemistry , Fluoroquinolones/toxicity , Aliivibrio fischeri/drug effects , Water Pollutants, Chemical/chemistry , Water Pollutants, Chemical/toxicity
17.
BMC Infect Dis ; 24(1): 763, 2024 Jul 31.
Article in English | MEDLINE | ID: mdl-39085804

ABSTRACT

BACKGROUND: One of the most prevalent bacteria that cause nosocomial infections is Pseudomonas aeruginosa. Fluoroquinolones (FQ) and aminoglycosides are vital antipseudomonal drugs, but resistance is increasingly prevalent. The study sought to investigate the diverse mechanisms underlying FQ and aminoglycoside resistance in various P. aeruginosa strains particularly during the COVID-19 crisis. METHODS: From various clinical and environmental samples, 110 P. aeruginosa isolates were identified and their susceptibility to several antibiotic classes was evaluated. Molecular techniques were used to track target gene mutations, the presence of genes encoding for quinolone resistance, modifying enzymes for aminoglycosides and resistance methyltransferase (RMT). Efflux pump role was assessed phenotypically and genotypically. Random amplified polymorphic DNA (RAPD) analysis was used to measure clonal diversity. RESULTS: QnrS was the most frequently encountered quinolone resistance gene (37.5%) followed by qnrA (31.2%) and qnrD (25%). Among aminoglycoside resistant isolates, 94.1% harbored modifying enzymes genes, while RMT genes were found in 55.9% of isolates. The aac(6')-Ib and rmtB were the most prevalent genes (79.4% and 32.3%, respectively). Most FQ resistant isolates overexpressed mexA (87.5%). RAPD fingerprinting showed 63.2% polymorphism. CONCLUSIONS: Aminoglycosides and FQ resistance observed in this study was attributed to several mechanisms with the potential for cross-contamination existence so, strict infection control practices are crucial.


Subject(s)
Aminoglycosides , Anti-Bacterial Agents , COVID-19 , Fluoroquinolones , Genotype , Microbial Sensitivity Tests , Phenotype , Pseudomonas Infections , Pseudomonas aeruginosa , Pseudomonas aeruginosa/genetics , Pseudomonas aeruginosa/drug effects , Pseudomonas aeruginosa/isolation & purification , Humans , Aminoglycosides/pharmacology , Egypt/epidemiology , COVID-19/epidemiology , Fluoroquinolones/pharmacology , Anti-Bacterial Agents/pharmacology , Pseudomonas Infections/microbiology , Pseudomonas Infections/epidemiology , SARS-CoV-2/genetics , SARS-CoV-2/drug effects , Drug Resistance, Bacterial/genetics , Hospitals , Random Amplified Polymorphic DNA Technique , Pandemics , Drug Resistance, Multiple, Bacterial/genetics
18.
Anal Chim Acta ; 1316: 342842, 2024 Aug 08.
Article in English | MEDLINE | ID: mdl-38969406

ABSTRACT

BACKGROUND: Fluoroquinolones (FQs) are widely used in livestock and poultry industry because of their satisfactory effects in preventing and treating bacterial infection. However, due to irrational use and poor biodegradability, FQs can easily remain in food animals and further enter the human body through the food chain. Therefore, accurate and sensitive detection of FQs residues in animal-origin food is significant. The traditional methods commonly used for FQs detection have some limitations. Ratiometric fluorescence detection technology has the advantages of fast, sensitive, self-correcting, and easy visualization. However, the reports on the use of ratiometric fluorescence probes for FQs detection are limited. RESULTS: In this work, a novel probe was proposed for ratiometric fluorescent analysis of FQs. In this probe, the fluorescence of dithioerythritol stabilized copper nanoclusters (DTE-Cu NCs) was significantly enhanced due to the Tb3+ triggered aggregation-induced emission effect. FQs bound Tb3+ in Tb3+/DTE-Cu NCs through carboxyl and carbonyl groups, so that Tb3+ was effectively sensitized to emit green fluorescence. However, the red fluorescence of DTE-Cu NCs was not interfered. The fluorescence of the probe transformed from red to green with the increase of FQs concentration. Using norfloxacin (NOR), difloxacin (DIF), and enrofloxacin (ENR) as FQs simulants, this probe showed a sensitive linear response ranged from 0.025 to 22.5 µM, with the limits of detection of 9.6 nM, 9.3 nM, and 7.7 nM. The application potential for FQs detection was verified via a standard addition assay of egg samples with the recovery rate of 90.4 %-114.7 %. SIGNIFICANT: The fluorescence probe based on Tb3+/DTE-Cu NCs is expected to realize the ratiometric fluorescence sensitive detection of FQs. The establishment of this simple, effective, and rapid detection platform opens up a new way for the detection of FQs residues in animal-origin foods, and also provides a new idea for the design of rapid detection platforms for other hazard factors.


Subject(s)
Copper , Fluorescent Dyes , Fluoroquinolones , Terbium , Copper/chemistry , Copper/analysis , Fluoroquinolones/analysis , Fluoroquinolones/chemistry , Fluorescent Dyes/chemistry , Terbium/chemistry , Spectrometry, Fluorescence , Metal Nanoparticles/chemistry , Animals , Limit of Detection
19.
Mikrochim Acta ; 191(8): 457, 2024 07 09.
Article in English | MEDLINE | ID: mdl-38980449

ABSTRACT

A new enantioselective open-tubular capillary electrochromatography (OT-CEC) was developed employing ß-cyclodextrin covalent organic frameworks (ß-CD COFs) conjugated gold-poly glycidyl methacrylate nanoparticles (Au-PGMA NPs) as a stationary phase. The resulting coating layer on the inner wall of the fabricated capillary column was characterized by scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FT-IR), energy dispersive spectroscopy (EDS), and electroosmotic flow (EOF) experiments. The performance of the fabricated capillary column was evaluated by CEC using enantiomers of seven model analytes, including two proton pump inhibitors (PPIs, omeprazole and tenatoprazole), three amino acids (AAs, tyrosine, phenylalanine, and tryptophan), and two fluoroquinolones (FQs, gatifloxacin and sparfloxacin). The influences of coating time, buffer concentration, buffer pH, and applied voltage on enantioseparation were investigated to obtain satisfactory enantioselectivity. In the optimum conditions, the enantiomers of seven analytes were fully resolved within 10 min with high resolutions of 3.03 to 5.25. The inter- to intra-day and column-to-column repeatabilities of the fabricated capillary column were lower than 4.26% RSD. Furthermore, molecular docking studies were performed based on the chiral fabricated column and as ligand isomers of analytes using Auto Dock Tools. The binding energies and interactions acquired from docking results of analytes supported the experimental data.


Subject(s)
Capillary Electrochromatography , Gold , beta-Cyclodextrins , Capillary Electrochromatography/methods , Gold/chemistry , beta-Cyclodextrins/chemistry , Stereoisomerism , Polymethacrylic Acids/chemistry , Amino Acids/chemistry , Amino Acids/analysis , Fluoroquinolones/chemistry , Fluoroquinolones/analysis , Metal Nanoparticles/chemistry , Metal-Organic Frameworks/chemistry , Molecular Docking Simulation
20.
Food Chem ; 459: 140419, 2024 Nov 30.
Article in English | MEDLINE | ID: mdl-39024876

ABSTRACT

Fluorescent nanoprobes are widely applied in innovate enzyme-linked immunosorbent assays (ELISA) for detection of fluoroquinolones (FQs) residue in foodstuffs. Nevertheless, the complicated synthesis of nanoprobes hampers their practical applications. Herein, a nanomaterial-independent and fluorescent ELISA for sensitive detection of FQs is developed using the Eu-micelles as signal probe. Non-nanostructured Eu-micelles with high quantum yield and stability are facilely synthesized through the assembly of Eu3+ and ligands. Alkaline phosphatase catalyzes hydrolysis of 4-nitrophenyl phosphate to 4-nitrophenol. The fluorescent Eu-micelles can be readily quenched by 4-nitrophenol via static quenching. The signal generation mechanism integrates well with conventional ELISA systems. The established fluorescent ELISA achieves sensitive detection of FQs with a limit of detection of 0.03 µg/kg. The validation results from LC-MS show that the fluorescent ELISA exhibits good accuracy and recoveries. Our study presents a nanomaterial-independent strategy for developing the rapid immunoassay for FQs, which holds good promise for practical applications.


Subject(s)
Chickens , Enzyme-Linked Immunosorbent Assay , Europium , Fluoroquinolones , Food Contamination , Limit of Detection , Nanostructures , Animals , Europium/chemistry , Food Contamination/analysis , Enzyme-Linked Immunosorbent Assay/methods , Fluoroquinolones/analysis , Fluoroquinolones/chemistry , Nanostructures/chemistry , Micelles , Meat/analysis , Immunoassay/methods , Fluorescent Dyes/chemistry , Anti-Bacterial Agents/analysis , Anti-Bacterial Agents/chemistry
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